PubMed Health⌕ Search

Biomedical subjects

M D van de Wetering

Publications and source records attributed to M D van de Wetering.

10 recordsLinked to original sources

The role of mannose-binding lectin (MBL) in paediatric oncology patients with febrile neutropenia.

Children with cancer often have fever during chemotherapy-induced neutropenia, but only some develop serious infectious complications. Mannose-binding lectin (MBL) deficiency might increase infection susceptibility in these children. MBL genotype and phenotype were prospectively determined in 110 paediatric oncology patients. During febrile neutropenia, MBL concentrations were measured longitudinally in time. MBL genotype and phenotype were correlated to clinical and laboratory parameters. Structural exon-1 MBL2 mutations and the LX promoter polymorphism lead to deficient MBL concentrations. The capacity to increase MBL concentrations during febrile neutropenia was associated with MBL2 genotype. Infectious parameters did not differ between MBL-deficient and MBL-sufficient neutropenic children (n = 66). In contrast, MBL-sufficient patients had a greater risk of Intensive Care admittance (Relative Risk 1.6, 95% Confidence Interval 1.3-2.0, P = 0.04). MBL-deficient neutropenic children did not have more severe infections. However, most patients (61%) were severely neutropenic (<100 cells/microL), compromising the opsonophagocytic effector function of MBL. MBL substitution might still be beneficial in patients with phagocytic activity.

Antineoplastic Combined Chemotherapy Protocols↗

Prophylactic antibiotics for preventing early Gram-positive central venous catheter infections in oncology patients, a Cochrane systematic review.

OBJECTIVE: Long-term tunnelled central venous catheters (TCVC) are increasingly used in oncology patients. Infections are a frequent complication of TCVC, mostly caused by Gram-positive bacteria. The objective of this review is to evaluate the efficacy of antibiotics in the prevention of early Gram-positive TCVC infections, in oncology patients. DATA SOURCES: We searched MEDLINE, EMBASE, and the Cochrane Controlled Trials Register up to July 2003. REVIEW METHODS: We selected randomised controlled trials (RCT) evaluating prophylactic antibiotics prior to insertion of the TCVC, and the combination of an antibiotic and heparin to flush the TCVC, in paediatric and adult oncology patients. The primary outcome was documented Gram-positive bacteraemia in patients with a TCVC. All trials identified were assessed and the data extracted independently by two reviewers. RESULTS: There were nine trials included. Four trials reported on vancomycin/teicoplanin prior to insertion of the TCVC compared to no antibiotics. There was no reduction in the number of Gram-positive TCVC infections with an Odds ratio of 0.42 (95% confidence interval 0.13-1.31). Five trials studied flushing of the TCVC with a vancomycin/heparin solution compared to heparin flushing only. This method decreased the number of TCVC infections significantly with an Odds ratio of 0.43 (95% CI 0.21-0.87). CONCLUSION: Flushing the TCVC with a vancomycin/heparin solution reduced the incidence of Gram-positive infections.

Anti-Bacterial Agents↗

Efficacy of oral prophylactic antibiotics in neutropenic afebrile oncology patients: a systematic review of randomised controlled trials.

The use of oral prophylactic antibiotics in oncology patients is still a matter of debate. A systematic review was performed to assess the evidence for the effectiveness of oral prophylactic antibiotics to decrease bacteraemia and infection-related mortality in oncology patients during neutropenic episodes. Medline, Embase and the Cochrane register of controlled trials were searched from 1966 until 2002. The main outcome was the number of patients with documented bacteraemia (Gram-negative or Gram-positive bacteraemia) and infection related mortality. Data-extraction and quality assessment were performed independently by two reviewers. A total of 22 trials met the inclusion criteria. Seventeen trials compared prophylaxis (quinolones or Trimethoprim/sulfamethoxazole (TMP/SMZ)) to no prophylaxis. The incidence of Gram-negative bacteraemia decreased significantly (pooled OR 0.39, 95% CI 0.24-0.62) without an increase in Gram-positive bacteraemia. Quinolone-based regimens showed a stronger reduction in Gram-negative bacteraemia while TMP/SMZ based regimens were more effective in Gram-positive bacteraemia. Infection related mortality due to bacterial causes decreased with the use of prophylactic antibiotics (pooled OR 0.49, 95% CI 0.27-0.88). No increase in fungaemia or fungal related mortality was seen with the use of oral prophylaxis. In conclusion, this study has shown that oral prophylactic antibiotics decreased Gram-negative bacteraemia and infection related mortality due to bacterial causes during neutropenic episodes in oncology patients.

Administration, Oral↗

Disseminated medullary thyroid carcinoma despite early thyroid surgery in the multiple endocrine neoplasia-2A syndrome.

A 51/2-year-old boy, with a family history of multiple endocrine neoplasia (MEN)-2A syndrome, was evaluated for presence of MEN-2A and medullary thyroid carcinoma (MTC). DNA diagnostics confirmed MEN-2A. Basal (360 ng/L) and pentagastrin stimulated (430 ng/L) calcitonin (CT) levels were slightly elevated, plasma carcinoembryonic antigen (CEA) was normal. Within a year both tumor markers increased and total thyroidectomy was performed. Histologic examination did not show MTC. In the following years, both tumor markers increased progressively but despite the use of multiple imaging techniques no metastases were localized. After 6 years, biopsy of a palpable lymph node showed MTC. The boy was treated with total cervical, suprahyoidal, and mediastinal lymph node dissection, showing MTC in almost all nodes. Again, the tumor markers remained high. At this point in time, the disadvantages of further medical interventions were outweighed against the chance for cure and it was decided to shift the goal of treatment toward palliation rather than cure. At the last visit the boy was clinically well with persistent extremely high levels of plasma CEA and CT. In conclusion, when prophylactic thyroidectomy in the MEN-2A syndrome has failed, it may be best to withdraw from further interventions to prevent more damage.

Biomarkers↗

Severity of enterocolitis is predicted by IL-8 in paediatric oncology patients.

Enterocolitis in oncology patients remains an important complication, but there is a lack of insight into its likely severity from microbial, pathological and inflammatory aspects. Paediatric oncology patients admitted with neutropenic fever, who developed abdominal pain and diarrhoea, were monitored by the takers of rectal biopsies, cultures, and inflammatory marker measurements. Twenty-five patients were included (mean age 7.1 years). 8 patients (32%) needed intensive care treatment, 3 (12%) patients died. Gram-positive bacteraemia was diagnosed in 4 patients (16%). Most patients had negative blood and stool cultures. Predictors of a severe clinical course of the enterocolitis were an increased serum interleukin-8 (IL-8) (>1000 pg/ml) level and an increased serum C-reactive protein level (CRP) (>150 mg/l) level, both measured on the first day of clinical illness. Relative risks (RR) for admission to an Intensive Care Unit (ICU) were 11.3 (95% Confidence Interval (CI) 1.6-77.9) for elevated IL-8 levels and 6.4 (95% (CI) 0.92-45.1) for increased CRP levels. Rectal biopsies and pathology could not predict outcome (P=0.22). IL-8 analysis at the onset of enterocolitis symptoms can identify high-risk patients, which might be used clinically to design future intervention trials.

Abdominal Pain↗

Pseudomembranous and neutropenic enterocolitis in pediatric oncology patients.

Neutropenic enterocolitis in oncological patients represents a wide spectrum of clinicopathological pictures each with its own entity. Early diagnosis of enterocolitis can lead to improved supportive care and therefore better outcome. We present two cases--patient A, a child with pseudomembranous colitis caused by Clostridium difficile, and patient B, a child with neutropenic enterocolitis, where no organism was found. By allowing an insight into the pathology, immunology and culture results, we demonstrated that early diagnosis leads to improved management and therefore improved outcome.

Adolescent↗

Prophylactic antibiotics for preventing early central venous catheter Gram positive infections in oncology patients.

BACKGROUND: Long-term tunnelled central venous catheters (TCVC) are increasingly used in oncology patients. Despite guidelines on insertion, maintenance and use, infections remain an important complication. Most infections are caused by Gram-positive bacteria. Therefore antimicrobial prevention strategies aimed at these micro-organisms could potentially decrease the majority of the TCVC infections. OBJECTIVES: To determine the efficacy of administering antibiotics prior to insertion of a TCVC with or without vancomycin/heparin flush technique in the first 45 days after insertion of the catheter to prevent Gram-positive catheter-related infections in oncology patients. SEARCH STRATEGY: We searched MEDLINE, EMBASE,and CENTRAL up to July 2001. Reference lists from relevant articles were scanned and conference proceedings were hand searched. The authors of eligible studies were contacted to obtain additional information. SELECTION CRITERIA: We selected randomized controlled trials giving prophylactic antibiotics prior to insertion of the TCVC, and trials using the combination of an antibiotic and heparin to flush the TCVC in oncology patients. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the studies for inclusion, extracted the data and assessed the quality. MAIN RESULTS: We included eight trials totalling 527 patients. Four reported on vancomycin/teicoplanin prior to insertion of the TCVC, and four reported on antibiotic flushing combined with heparin. The overall effect of an antibiotic prior to catheter insertion decreases the number of Gram-positive TCVC infections (odds ratio [OR] = 0.55, 95% confidence interval [CI] 0.29 to1.04). Given an expected infection rate of TCVC during the first 45 days of up to 30% this OR implies that the number needed to treat (NNT) will be 10 (95% CI 4 to13), this means vancomycin needs to be given to 10 patients to prevent one TCVC infection. Flushing the TCVC with antibiotics and heparin proved to be beneficial (OR = 0.35, 95% CI 0.16 -to 0.77). For intraluminal colonization the baseline infection-rate is 15% which leads to a NNT of 13 (95% CI 5 to 23). REVIEWER'S CONCLUSIONS: Both interventions lead to a positive overall effect but should be considered with care due to the small number of studies. Depending on the baseline TCVC infection rate it is justified to administer antibiotics prior to the TCVC insertion or to flush the catheter with a combination of an antibiotic and heparin, if the catheter-related infection rate is high.

Antibiotic Prophylaxis↗

Bacteraemia in a paediatric oncology unit in South Africa.

OBJECTIVES: To identify the morbidity and mortality due to infections in a South African paediatric oncology unit, and to identify risk factors associated with first bacteraemic episodes in this unit. PROCEDURE: A retrospective cohort study was done in a large regional referral paediatric cancer centre from 1991-1995, of all consecutive patients with culture proven bacteraemia. Eighty-three oncology patients were studied (median age 4.0 years) in whom a total of 200 episodes of bacteraemia were recorded, of which 83 first bacteraemic episodes. RESULTS: Of the 200 episodes 70% were caused by Gram-positive organisms, 20% by Gram- negative organisms and 10% by fungal organisms. Organisms associated with high mortality were Gram-negative organisms (Acinetobacter spp., Pseudomonas aeruginosa, Klebsiella species), and fungal organisms, (Candida parapsilosis). Seventeen out of 200 episodes ended in death of the patient. In 59% of patients Hickman catheters were in situ. The mean incidence of catheter related bacteraemia's was 3.3 episodes per 1000 catheter days. Seventy percent of first bacteraemic episodes occurred within 50 days after placement of the catheter. The generalized estimation equations model revealed that more Gram-negative infections occurred in the presence of a Hickman catheter (odds ratio 2.2, 95% CI 1.0-5.0). The presence of neutropenia and the use of parenteral nutrition were not associated with specific bacteraemic patterns. CONCLUSIONS: Including all bacteraemic episodes in this cohort study a high incidence of fungal infections occurred of which 64% occurred with a Hickman catheter in situ. Candida parapsilosis had a higher incidence than reported in other centres. Secondly looking at first bacteraemic episodes a high incidence of Gram-negative infections was observed especially in the presence of a Hickman catheter.

Adolescent↗